Pancreatic cancer shows a wide range of geographic incidence variation with Louisiana wetlands and the Mississippi delta regions having the highest rates in the U.S. Pancreatic cancer has not been widely reported in developing countries, but one area of high incidence is the northeast Nile delta region of Egypt. Egypt and Louisiana provide similar environmental settings for comparison and possible understanding of the etiology of pancreatic cancer, and thus, having begun preliminary observations in these areas, we propose to expand them to investigate possible association of elevated rates with exposure to cadmium in the wetlands and the Mississippi delta regions. We propose a case-case comparison of 2 groups of pancreatic cancer patients; a) a group experiencing presumed high cadmium exposure in Louisiana, and b) a group experiencing presumed low exposure to cadmium and average incidence of pancreatic cancer in Michigan. The first aim of the study is to measure tumor and urinary levels of cadmium in 100 pancreatic cancer patients from Louisiana (n=50) and Michigan (n=50). We will test the hypothesis that pancreatic cancer patients in the Mississippi delta and wetlands in Louisiana have higher tumor and urine cadmium levels than patients from Michigan. The second aim is to further characterize K-ras mutations in all pancreatic cancer tumors. Our preliminary findings from the U.S. and Egypt showed a high rate of GTT K-ras mutations in patients with high cadmium levels in Egypt. We will confirm our findings by characterizing the spectrum of K-ras and p53 mutations in all patients included in the proposed study. This study will help determine whether high tissue and urine cadmium or other heavy metal levels are associated with increased risk for pancreatic cancer in polluted regions in Louisiana. The results from this study will provide clues about the etiology of pancreatic cancer. [unreadable] [unreadable] [unreadable]